ArticleAmerican journal of physiology. Cell physiology2008
Cytoplasmic cAMP concentrations in intact cardiac myocytes.
Article in American journal of physiology. Cell physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 90 citations in OpenAlex.
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- Red blood cell signaling is functionally conserved iniScience · 2024Article
- A multiscale predictive digital twin for neurocardiac modulation.The Journal of physiology · 2023Article
- Allosteric modulation of ryanodine receptor RyR1 by nucleotide derivatives.Structure (London, England : 1993) · 2023Article
- A-Kinase Anchoring Proteins in Cardiac Myocytes and Their Roles in Regulating Calcium Cycling.Cells · 2023Review
- Green fluorescent cAMP indicator of high speed and specificity suitable for neuronal live-cell imaging.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A multiscale model of the regulation of aquaporin 2 recycling.NPJ systems biology and applications · 2022Article
- Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts.International journal of molecular sciences · 2022Review
- Compartmentalized cAMP signaling in cardiac ventricular myocytes.Cellular signalling · 2022Review
- Mechanisms of cAMP compartmentation in cardiac myocytes: experimental and computational approaches to understanding.The Journal of physiology · 2021Review
- Mitochondrial A-kinase anchoring proteins in cardiac ventricular myocytes.Physiological reports · 2021Article
- Transcription factors regulated by cAMP in smooth muscle of the myometrium at human parturition.Biochemical Society transactions · 2021Review
- Compartmentation of βBritish journal of pharmacology · 2021Article
- Article
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- cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells.Nature communications · 2020Article
- "Heart Oddity": Intrinsically Reduced Excitability in the Right Ventricle Requires Compensation by Regionally Specific Stress Kinase Function.Frontiers in physiology · 2020Review
- Dual Activation of cAMP Production Through Photostimulation or Chemical Stimulation.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Effect of Adenylyl Cyclase Type 6 on Localized Production of cAMP byThe Journal of pharmacology and experimental therapeutics · 2019Article
- Establishing a Split Luciferase Assay for Proteinkinase G (PKG) Interaction Studies.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
In cardiac myocytes there is evidence that activation of some receptors can regulate protein kinase A (PKA)-dependent responses by stimulating cAMP production that is limited to discrete intracellular domains. We previously developed a computational model of compartmentalized cAMP signaling to investigate the feasibility of this idea. The model was able to reproduce experimental results demonstrating that both beta(1)-adrenergic and M(2) muscarinic receptor-mediated cAMP changes occur in microdomains associated with PKA signaling. However, the model also suggested that the cAMP concentration throughout most of the cell could be significantly higher than that found in PKA-signaling domains. In the present study we tested this counterintuitive hypothesis using a freely diffusible fluorescence resonance energy transfer-based biosensor constructed from the type 2 exchange protein activated by cAMP (Epac2-camps). It was determined that in adult ventricular myocytes the basal cAMP concentration detected by the probe is approximately 1.2 muM, which is high enough to maximally activate PKA. Furthermore, the probe detected responses produced by both beta(1) and M(2) receptor activation. Modeling suggests that responses detected by Epac2-camps mainly reflect what is happening in a bulk cytosolic compartment with little contribution from microdomains where PKA signaling occurs. These results support the conclusion that even though beta(1) and M(2) receptor activation can produce global changes in cAMP, compartmentation plays an important role by maintaining microdomains where cAMP levels are significantly below that found throughout most of the cell. This allows receptor stimulation to regulate cAMP activity over concentration ranges appropriate for modulating both higher (e.g., PKA) and lower affinity (e.g., Epac) effectors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.